Organisms that adhere to, for example, the catheter surface maintain themselves by producing an “extracellular slime,” a substance rich in exopolysaccharides, often referred to as fibrous glycocalyx or microbial biofilm. Microorganisms bind to the surface of host proteins, such as fibrin and fibronectin, to produce biofilm. The organisms embed themselves in the biofilm layer become more resistant to antimicrobial agents and therapies. The use of lumen flush solutions including a combination of antimicrobial agents as well as anti-coagulants is a known process for removing them.
Another strategy has been to impregnate the surfaces of said catheters with antimicrobial agents in order to prevent colonization and the formation of biofilm. An improved approach for prevention of intravascular catheter-related infections is desired.
A considerable amount of attention and study has been directed toward preventing colonization of bacterial and fungal organisms on the surfaces of orthopedic implants by the use of antimicrobial agents, such as antibiotics, bound to the surface of such devices. The objective of such attempts has been to produce a sufficient bacteriostatic or bactericidal action to prevent colonization. Various methods have previously been employed to coat the surfaces of medical devices with an antibiotic.
U.S. Pat. No. 4,442,133, invented by Greco et al., discloses a method to coat the surface of medical devices with antibiotics involving first coating the selected surfaces with benzalkonium chloride followed by ionic bonding of the antibiotic composition.
U.S. Pat. No. 4,879,135, invented by Greco et al., discloses surface modification of surgical implants by binding of drugs which, after implantation, are slowly released. More particularly, it relates to improved surgical implants having sustained, localized delivery of pharmacological agents such as extended antibiotic activity or reduced thrombogenicity, and methods for producing same. The surface modification of surgical implants by the adhesion thereto of pharmacological agents for the purpose of minimizing infection and prosthesis rejection is well-known and has generated broad interest for some time.
A biofilm is an accumulation of microorganisms including bacteria, fungi and viruses that are embedded in a polysaccharide matrix and adhere to solid biologic and non-biologic surfaces. Biofilms are medically important as they may account for a majority of microbial infections in the body. Biofilms account for many of the infections of the oral cavity, middle ear, indwelling catheters and tracheal and ventilator tubing.
Biofilms are remarkably resistant to treatment with conventional topical and intravenous antimicrobial agents. This is thought to be due to the antibiotic's inability to penetrate the polysaccharide coating of the biofilm.
Bacteria and other microorganisms embedded within biofilms are also resistant to both immunological and non-specific defense mechanisms of the body. Bacterial contact with a solid surface triggers the expression of a panel of bacterial enzymes that cause the formation of polysaccharides that promote colonization and protection of the bacteria.
The polysaccharide structure of biofilms is such that immune responses may be directed only at those antigens found on the outer surface of the biofilm and antibodies and other serum or salivary proteins often fail to penetrate into the biofilm.
Also, phagocytes may be effectively prevented from engulfing a bacterium growing within a complex polysaccharide matrix attached to a solid surface.
Many different medical devices may lead to infection when in contact with a body tissue or fluid. Exemplary of such devices are vascular access (arterial and venous) catheters, introducers, vascular grafts, urinary catheters and associated devices, such as drainage bags and connectors, and abdominal cavity drainage tubing, bags and connectors, and many others.
WO200289750 relates to a photodynamic therapy utilizing a pyrrolnitrin. In particularly, it relates to improved surgical implants having sustained, localized delivery of pharmacological agents such as extended antibiotic activity or reduced thrombogenicity, and methods for producing same. More particular, it discloses a method of photoeradication of cells and acellular organisms, such as during an in vitro or in vivo disinfection or sterilization procedure, or for cancer cell or acellular organism eradication. In one embodiment, the method utilizes a combination of a photosensitive material, pyrrolnitrin, and a chemical agent, such as a surfactant material, in a solution. In accordance with this international patent application, a photodynamic therapy utilizing a photosensitive material, such as methylene blue, methylene green, or toluidene blue, in combination with pyrrolnitrin, and a light emitting device, such as a light wand, light patch, light pad or shaped light-emitting or light-communicating article is described.
The nanoparticles are used widely at present, especially in the field of nanotechnology for biomedical treatment. These nanoparticles need to reach the pathological region and go through extremely small holes inside the body. For example, if it is necessary to transport the gold nanoparticles to malignant tumors through holes of approximately 100 nm formed at the connection branch points between the pre-existing blood vessels and the new blood vessels produced by those malignant tumors. The rod-shaped gold nanoparticles will encounter difficulties reaching the area of pathology due to their shape.
The European Patent No. EP2241394 discloses a gold nanoparticle composition that can pass through small holes in vivo more readily than a rod-shaped gold nanoparticle, and that can be utilized as a self-heating energy acceptor.
The International Patent Application No. WO2009/024636 relates to a photothermal treatment. More particularly, it discloses an encapsulated hybrid material. That encapsulation in silica is particularly advantageous in the measurement to control the textural parameters of the cover and at the same time offers many opportunities for functionalization. It is especially suitable for the incorporation of gold nanoparticles in a mesoporous silica matrix, which allow a high pore management with controllable pore size and high surface area. The hybrid material allows the anchor of a drug and/or biomarker on the surface of silica that forms the nanospheres. The hybrid material contains at least two components: gold nanoparticles, of size between 10 and 60 nm, within a matrix of an inorganic compound, preferably silicon. The light absorbed by the nanoparticles is rapidly converted into heat. The incorporation of two or more gold nanoparticles within a capsule involves the interaction between them against electromagnetic stimuli which allows their use as diagnostic tools, control of drug release or photothermal treatments.
The patent application US20130018299 discloses nano-constructs comprising nanoshells and methods of using the nano-constructs for treating or ameliorating a medical condition. More particularly, a method of forming degradable nanoshells on a polymeric core substrate is described. The nanoshells include a metal, carbon, or a conducting polymer. The nano-constructs can be administered to a target tissue of a subject, which can be human or an animal. An energy source can be applied to the nano-constructs. The nano-constructs absorb the energy and then translate the energy into heat, thereby providing therapy via delivering a drug contained into said nano-constructs to the subject. The light activates the drug delivery.
The International patent application WO2010/107720 describes a system for energy upconversion and/or down conversion and a system for producing a photostimulated reaction in a medium. The nanoparticle described is configured, upon exposure to a first wavelength λ1 of radiation, to generate a second wavelength λ2 of radiation having a higher energy than the first wavelength λ1. The system is designed for producing a photostimulated reaction in a medium. Furthermore, that system includes a receptor disposed in the medium in proximity to the nanoparticle which, upon activation by the second wavelength λ2, generates the photostimulated reaction. Therefore, again the emission light (Δ2) causes the activation of a determinate reaction. Thus, these particles are configured to convert the incident light into a different emitted light.
Therefore, it is still the need to provide a novel way of infection prevention, biofilm inhibiting and/or biofilm destroying which will be adequate for any type of substrate, which properties will be maintained for a long term, and specially without delivering an antimicrobial agent nor a pharmaceutical agent such as an antibiotic or a drug, respectively.